The present invention relates to a novel medicinal herbal composition and its use for treating patients with immunological disorders, particularly IgE mediated diseases, which include, but are not limited to, allergic rhinitis, allergic conjunctivitis, allergic asthma, atopic eczema, atopic dermatitis, food allergy, hyper IgE syndrome, and rheumatoid arthritis. The novel medicinal herbal composition contains aqueous extracts of Tuber ophiopogon, Tuber pinelliae, Radix glycyrrhizae, Herba tridacis procumbentis, and Radix pancis quinquefolii. The present invention also relates to a method for making the medicinal herbal composition and methods for treating patients with the medicinal herbal composition.
Antigen-induced, particularly allergen-induced immunological disorders, such as asthma, has long been known as one of the serious health problems in the world. Allergy in one form or another afflicts more than 20% of the world population. In recent years, statistics shows that the onset of the allergic-related immunological disorders has shifted to the younger population, which means that more children and/or adolescents have developed symptoms of allergen-induced immunological disorders. For instance, in Taiwan, the prevalence of childhood asthma increased from 1.3% in 1974, to 5.07% in 1985, and to 5.8% in 1991. Also, allergic rhinitis increased from 7.84% in 1985 to 20.67% in 1991. Furthermore, atopic eczema was 1.43% in 1974 and 1.23% in 1985, in 1991, it was 3.84%. It is believed that the early onset of allergen-related immunological disorders are likely due to environmental pollution.
Respiratory allergies are immunoglobulin E (IgE)-mediated immune response. (See Brinker, J. Naturopathic Medicine, (1993):4:64-68). There are two major types of respiratory allergic reactions: The immediate hypersensitivity reactions include allergic rhinitis (hay fever) and allergic (extrinsic) bronchial asthma. Allergic rhinitis is brought on by antigen/IgE binding to sensitized mast cells and basophils, causing a decrease in cAMP which leads to release of esosinophil chemotactic factor and histamine. Histamine binding to H1-receptors has several results. It increases vasodilation, capillary permeability, and smooth muscle contraction, manifesting as nasal congestion with watery discharge, sneezing, and itching eyes.
Allergic asthma is another IgE-mediated immune response in which mast cells release histamine, bradykinin, and arachidonic acid metabolites including the leukotriene slow reacting substances of anaphylaxis and thromboxane/ prostaglandin bronchoconstrictors. Platelet activating factor is another potent asthma mediator released from a number of leukocytes. In this condition, histamine, which released after a decrease in cAMP, acts on H1-receptors to cause bronchospasm. It is also responsible for bronchoconstriction due to cholinergic reflex action and half of the prostaglandin generation in anaphylaxis.
While the percentage of affected population and severity of the diseases are rising, current methods for treating allergy still primarily depend on empirical and serendipitous findings rather than from scientific approach. At present, most patients are treated with drugs that aim at controlling symptoms resulted from the release of mediators by effector cells. Although some drugs appear to be effective in short term and with few occurrences of adverse effects, long term effects for preventing disease progression and permanent destruction are still largely unknown. For example, long-term oral therapy, such as steroid therapy, for treating asthma, is now known to be associated with multiple debilitating effects such as growth delay, osteoporosis, and adrenal suppression.
Traditional Chinese herbs and medicinal combinations have been known for improving function of immune system and treating various chronicle immunological disorders. For example, Hamasaki et al., J. Ethnopharmacology, (1997) 56:123-131, disclose a Chinese herbal medicine, Shinpi-To, which inhibits IgE-mediated leukotriene synthesis in rat basophilic leukemia-2H3 cells. Shinpi-To is a freeze-dried granular Chinese herbal medicine prepared from extract of seven (7) medicinal herbs, i.e., Ephedrae herba (Ephedra sinica Stapf), Armeniacae semen (Prunus armeniaca Linne), Magnoliae cortex (Magnolia obovata Thunberg), Aurantii nobilis Pericarpium (Citrus unshiu Markovich), Glycyrrhizae radix (Glycyrrhiza uvalensis Fischer), Bupleuri radix (Bupleurum falcatum L.), and Perillae herba (Perilla frutescens Britton var. acuta Kudo). Shinpi-To is useful for treating childhood asthma.
Toda et al., J. Ethnopharinacology, (1988) 24:303-309, discloses a Chinese herbal medicine, Saiboku-To, which shows inhibitory effects on histamine release from mouse peritoneal mast cells. Saiboku-To is useful for treatment of asthma. Saiboku-To contains ten medicinal herbs: Bupleurum falcatum L., Pinellia ternata Breitenbach, Poria cocos Wolf, Scutellaria baicalensis Georgi, Zizyphus vulgaris Lam., Panax ginseng C. A. Meyer, Magnolia oborata Thumberg, Glycyrrhiza glabra L., Perilllae frutescens Britton var. acuta Kudo, and Zingiber officinale Roscoe.
Li et al., Immunopharmacology, (1999), 43:11-21, discloses a Chinese herbal medicine, Hochu-Ekki-To, which shows effects on restoring stress-induced immunosuppression. Hochu-Ekki-To consists often (10) ingredients, i.e., Ginseng Rx., Atractylodis alba Rz., Astragali Rx., Angelicae sinensis Rx., Jujubae Fr., Citri reticulatae Pc., Bupleuri Rx., Glycyrrhizae Rx. Preparata, Zingiberis recens Rz., and Cimicifugae Rz.
Zou et al., Chinese Traditional and Western Medical Magazine, (1996):529-532, discloses a Chinese herbal medicine, Wenyang Tongluo mixture, for treating cold-type asthma patients. It shows effects on improving pulmonary ventilation functions, regulating adrenergic xcex2-receptors of peripheral blood lymphocytes, and decreasing the serum level of 5-hydroxytryptamine. Wenyang Tongluo mixture contains twelve (12) medicinal herbs, i.e., Red Ginseng, Zhi Fu Pian, Yin Yang Huo, Dried Ginger (Zingiberis recens Rz.), Zhi Huang Zhi, Angelicae sinesis Rx., Ephedra, Polygalae Rx., Sang Baipi, Sheng Shi Gao, Schisandrae Fr., and Licorice (Glycyrrhizae Rx. Preparata).
There is also an ophiopogon decoction disclosed on the internet (www.herb.com.tw) which shows a combination of six (6) herbs, i.e., Ophiopogonis Rx., Pinelliae Rz. Preparata, Oryzae Sm., Jujubae Fr., Ginseng Rx., and Glycyrrhizae Rx. It is useful for treating bronchitis and bronchial asthma.
In dealing with Chinese herbal medicine, it is critical to control the quality of the herbs, because the contents and/or active ingredients of the herbs can vary significantly due to herb""s growing conditions and harvesting seasons/techniques. If any of the critical conditions and factors, such as the locality where the herbs are grown, the season(s) when the herbs can be harvested, and the manufacturing process of the herb, are not met, the effectiveness of the herbal medicine would vary. So far, there has been no report showing the adoption of any reliable scientific method for monitoring the quality of the Chinese herbal medicine.
The present invention provides novel and non-toxic pharmaceutical compositions derived from herbs, which are primarily found in China and Taiwan. The combined use of these herbs has never been found in any literatures or reports. These pharmaceutical compositions are particularly effective in treating patients with immunological disorders, especially IgE mediated diseases. The pharmaceutical compositions of the present invention have demonstrated special effects on down-regulation of the synthesis of interleukin 4 (IL-4) and suppression of IgE. In addition, to effectively control the quality of the herbs, the present invention fingerprints each herb using thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) to ensure that each herb used in the composition contains consistent and reproducible ingredients.
The present invention provides a pharmaceutical composition which is effective in treating patients with immunological disorders, including, but not limited to, allergic rhinitis, allergic conjunctivitis, allergic asthma, atopic eczema, atopic dermatitis, food allergy, hyper IgE syndrome, and rheumatoid arthritis.
The pharmaceutical composition contains aqueous extracts of Tuber ophiopogonis (ophiopogon), Tuber pinelliae (pinellia), Radix glycyrrhizae (raw licorice), Radix pancis quinquefolii (American ginseng) and Herba tridacis procumbentis (lantern tridax). Ophiopogon, pinellia, raw licorice, and American ginseng are preferably extracted in water. Lantern tridax is preferrably extracted in alcohol, more preferably in 50% alcohol. The preferred weight ratio of ophiopogon, pinellia, raw licorice, American ginseng and lantern tridax is about 3:2:1:1:1.
Each of the aqueous extracts of ophiopogon, pinelliae, raw licorice, American ginseng and lantern tridax is preferably separately filtered and condensed. The solid content of the condensate of ophiopogon constitutes about 20-30% by weight, preferably about 25% by weight, of the ophiopogon raw material. The solid content of the condensate is the condensate excluding the water. In the case of ophiopogon, the condensate contains substantial amount of water (i.e., about 58% of the condensate of ophiopogon is water). The solid contents of the rest of the herbs are about the same as the condensate (i.e., the water content was insignificant). The condensate of pinellia constitutes about 15-25% by weight, preferably about 20% by weight, of the pinellia raw material. The condensate of raw licorice constitutes about 15-25% by weight, preferably about 20% by weight, of the raw licorice raw material. The condensate of American ginseng constitutes about 19-29% by weight, preferrably about 24.3% by weight, of American ginseng raw material. The condensate of lantern tridax constitutes about 5-10% by weight, preferably about 7.8% by weight, of lantern tridax raw material.
Except for ophiopogon which is not granulated, each of the condensates of pinellia, raw licorice, American ginseng, and lantern tridax are individually granulated to form individual granules. Before granulation, an excipient, preferably corn starch, is added to the condensate to confer a suitable form of the granules. The individual granules and the condensate of ophiopogon are then mixed together to form mixed granules, which are then encapsulated.
The granules of pinellia constitute about 20-30% by weight, preferably about 25% by weight, of the pinellia raw material. The granules of raw licorice constitute about 16-26% by weight, preferably about 21% by weight, of the raw licorice material. The granules of American ginseng constitute about 27-37% by weight, preferably about 32% by weight, of the American ginseng raw material. The granules of lantern tridax constitute about 37-47% by weight, preferably 42% by weight, of the lantern tridax raw material.
The present invention also provides a method of making the pharmaceutical composition. The method requires an extraction of ophiopogon, pinellia, raw licorice, American ginseng and lantern tridax individually. Ophiopogon, pinellia, raw licorice, and American ginseng are extracted in water by decocting. Lantern tridax is extracted in alcohol, preferably 50% alcohol, by refluxing. After the extraction, each individual extract is filtered to remove the remaining herb. The fitrate is then condensed by decompressed condensation at a temperature of about 55xc2x0 C. and a vacuum of about 30 torr to form a condensate. An adequate amount of an excipient, preferably corn starch, is added to each of the condensate, except ophiopogon, to form an extraction paste, which is subject to granulation by spray-drying at an inlet temperature of about 105xc2x0 C. and an outlet temperature of about 76-77xc2x0 C. The respectively granules from pinellia, raw licorice, American ginseng, and lantern tridax are mixed with the condensate of ophiopogon to form the mixed granules, which can be encapsulated.
In addition, the ratio of aqueous extractant (by volume) to herb (by weight) is about 20:1. For water extraction, the preferable decocting time is about 30 minutes. The preferred alcohol extraction time is also about 30 minutes.
The pharmaceutical composition of the present invention, although containing the same five herbal mixture as in the parent application, differs from the parent composition in that the composition of the present invention contains aqueous extracts from the herbs, while the parent composition contains primarily powders of the herbs (except ophiopogon, which is also from the aqueous extract). The present pharmaceutical composition demonstrates better effects in terms of drug efficacy and efficiency than the parent composition, possibly due to the release of active ingredients from the extraction procedures.